Visceral pain: the ins and outs, the ups and downs

Abstract

Purpose of review: Visceral pain represents a major clinical problem, yet far less is known about its mechanisms compared with somatic pains, for example, from cutaneous and muscular structures.

Recent findings: In this review, we describe the neuroanatomical bases of visceral pain signalling in the peripheral and central nervous system, comparing to somatic pains and also the channels and receptors involved in these events. We include an overview of potential new targets in the context of mechanisms of visceral pain and hypersensitivity.

Summary: This review should inform on the recognition of what occurs in patients with visceral pain, why comorbidities are common and how analgesic treatments work.

Figure 1. Innervation of the rat GI tract

Some visceral afferents innervating organs in thoracic and abdominal cavities travel either along the vagus nerve with cell bodies in the nodose ganglion (NG) and central terminals in the nucleus tractus solitarii (NTS), or along the dorsal column pathway (dotted line) with cell bodies in dorsal column nuclei (DC) in the brainstem. Other afferents innervating the same organs have terminals in the spinal cord, before passing through pre- and/or paravertebral ganglia en route with cell bodies in dorsal root ganglia (not illustrated; (23)). Straight lined pathways indicate sympathetic innervation and hyphenated pathways indicate parasympathetic innervation. (Prevertebral ganglia- CG: coeliac ganglion; SMG: superior mesenteric ganglion; IMG: inferior mesenteric ganglion; PG: pelvic ganglion. Nerves- S1, S2, S3, S4: greater, less, least and lumbar splanchnic nerves, respectively; IMN: intermesenteric nerve; HGN: hypogastric nerve; PN: pelvic nerve (adapted from (23)).

Figure 2. Ascending pathways from spinal cord neurones in visceral nociception (in rodents)

Ascending projections from lamina I neurones in the spinal cord travel along the spinoparabrachial pathway to the parabrachial nuclei (PB) with ensuing projections to the amygdala (Am) and hypothalamus (Hyp), whereas projections from deep dorsal horn neurones travel along the spinothalamic tract to thalamic nuclei (VPM and VPL), with further projections to the insula, somatosensory cortex and prefrontal cortex. Neurones from lamina III-IV and X can also travel along the post-synaptic dorsal column with medullary cell bodies, with further projections to thalamic nuclei (LC, locus coeruleus; Po, posterior thalamic nuclei; CC, cingulate cortex; CN: cuneate nucleus; GN: gracile nucleus; adapted from (40).

Figure 3. Descending pathways in nociception (in rodents)

Descending projections from higher centres are integrated in the midbrain and brainstem. Inhibitory controls from the locus coeruleus complex (A5, locus coeruleus, A7) are mediated by pre- and postsynaptic α₂-adrenergic receptors in the dorsal horn. Descending controls from the RVM can be both inhibitory and facilitatory, although one facilitatory pathway is mediated by presynaptic 5-HT₃ receptors (Am: amygdala; Hyp: hypothalamus; VPM and VPL: thalamic nuclei; Po: posterior thalamic nuclei; CC: cingulate cortex; LC: locus coeruleus; PAG: periaqueductal grey; RVM: rostral ventromedial medulla; adapted from (40).